This research will probe the molecular basis of erythrocyte membrane elasticity and failure in shear deformation by measuring the effect of various alterations in molecular structure on the continuum mechanical properties of the membrane. The relevant material properties include the surface elastic shear modulus, the yield shear resultant, the plastic viscosity and the rate of material relaxation (creep viscosity). These material properties will be quantified using established micromechanical techniques. The elastic shear modulus and rate of material relaxation will be measured by micropipette aspiration; the yield shear resultant and plastic viscosity will be measured by the flow channel technique. Alterations in molecular structure will be accomplished by changing temperature and ionic strength and by introducing antibodies specific to the membrane structural proteins. In addition to these induced changes several naturally occurring membrane abnormalities will be investigated. Some preliminary work has been completed on the mechanical properties of hereditary spherocytes, and abnormal values for the elastic shear modulus and the yield shear resultant have been measured. In addition, two other abnormal cell types will be investigated: irreversibly sickled cells (ISC) and hereditary elliptocytes. One of the long range goals of this research will be to use the micromechanical data to develop quantitative molecular models which are consistent with the available biochemical data and which account for the observed continuum mechanical behavior. These results will contribute to the understanding of the membrane defect in hereditary spherocytosis and possible defects to be found in hereditary elliptocytosis and irreversibly sickled cells.